Infection by the human immunodeficiency virus (HIV) has grown to epidemic proportions, affecting about one to two million persons in the United States, and about eight to ten million persons worldwide. Lymphocytes having the CD4 antigen on their surface appear to be the major target of this virus. HIV-infected CD4-positive lymphocytes have been reported to be located in the peripheral blood, the lymph nodes and other internal lymphoid organs.
Enumeration of CD4-positive cells in the peripheral blood has been the most widely used test for monitoring HIV-induced immune dysfunction, as well as serving as a surrogate marker for evaluating anti-viral drug efficacy. The peripheral blood CD4 cell count, however, has been reported to have only limited usefulness. It is now believed that major functional alterations in immunity may be unrecognized by peripheral blood CD4 cell enumeration alone. For example: (i) there is considerable day to day variability in peripheral blood CD4 counts within a given individual; (ii) peripheral blood CD4 counts do not provide information about lymphocyte function; (iii) the peripheral blood comprises only about 2-5% of the total body lymphoid tissue; and (iv) important changes in CD4 cell trafficking and distribution may not be represented by measurements that sample only the peripheral blood. In addition, serial determination of CD4 levels as a marker for anti-viral drug efficacy has been reported to give disappointing results, i.e., maintenance or elevations in CD4 cell counts achieved in association with antiviral therapy have often not been predictive of prolonged life or decreased incidence of opportunistic infection.
The presence of lymphocytes in the lymphoid organs can be determined in certain situations using the technique of biopsy. Biopsy, however, is only of limited value because it generally cannot be used routinely and generally is restricted to easily-accessible lymph nodes.
Thus, there is a compelling need for a non-invasive test that can assess immune function, and that can provide an index of the totality of lymphocyte distribution and trafficking throughout the body, i.e., in other tissues as well as the peripheral blood.
There also is a need for such a test in evaluating individual patients with autoimmune diseases, particularly those in which immunomodulating therapy might be useful, e.g., rheumatoid arthritis or multiple sclerosis, or in patients with certain infections or malignancies.